Developing Theronostic Nanoparticles as CT Contrast Agent and Chemodrug Carrier for Lung Cancer Application via Inhalation Delivery

Lung cancer continues to be a leading cause of death around the world. Early detection can improve 5 year survival rate for lung cancer patient. The computed tomography (CT) is one of the most frequently used hospital diagnostic tools and also one of the most cost-effective. The combination of nanotechnology and molecular biology has developed into an emerging research area for provide superior image quality by using nanoparticles as contrast agent. Iodine element has stronger X-ray mass attenuation coefficient than gold at low voltage, therefore iodine based contrast agent (Iohexol) is more suitable for low dose CT using. In this study, a novel theronostic gelatin nanoparticle composed of Iohexol and chemodrug (cisplatin) is synthesized for lung cancer early diagnosis and treatment simultaneously. Hyrounic acid (HA) is covered on the particle surface for targeting to the CD44 receptor which overexpressed on the lung cancer cells. Finally, these particles are transported directly into the lung via inhalation delivery which can effectively enhance the CT image contrast, and increase drug concentration in lung for inhibited cancer cells growth. The plan is a three-year’s project, the annual goal of each year is: (1) synthesis and characterization of the theronostic nanoparticles (gelatin-Iohexol-cisplatin complexes nanoparticle with HA modified on the surface, abbreviated as GP-IPt-HA), (2) the in vitro test for anti-cancer effect and molecular mechanism examination, and (3) the diagnosis and therapeutic effect of the GP-IPt-HA NPs confirmed in a lung cancer mice model via inhalation. In this respect, this theronostic nanoparticles system would be a promising inhalation agent with CT image improvement for diagnosis and long-term sustained-release characteristics for the treatment of lung tumors in the future.